A sparse additive model for high-dimensional interactions with an exposure variable

A conceptual paradigm for onset of a new disease is often considered to be the result of changes in entire biological networks whose states are affected by a complex interaction of genetic and environmental factors. However, when modeling a relevant phenotype as a function of high dimensional measurements, power to estimate interactions is low, the number of possible interactions could be enormous and their effects may be non-linear. A method called sail for detecting non-linear interactions with a key environmental or exposure variable in high-dimensional settings which respects the strong or weak heredity constraints is proposed. It is proven that asymptotically, sail possesses the oracle property, i.e., it performs as well as if the true model were known in advance. A computationally efficient fitting algorithm with automatic tuning parameter selection, which scales to high-dimensional datasets is proposed. Simulation results show that sail outperforms existing penalized regression methods in terms of prediction accuracy and support recovery when there are non-linear interactions with an exposure variable. sail is applied to detect non-linear interactions between genes and a prenatal psychosocial intervention program on cognitive performance in children at 4 years of age. Results show that individuals who are genetically predisposed to lower educational attainment are those who stand to benefit the most from the intervention. The proposed algorithms are implemented in an R package available on CRAN (https://cran.r-project.org/package=sail).